Division of Cardiovascular Medicine, Department of Medicine
Amino Acids, Peptides, and Proteins | Biological Factors | Cardiology | Cardiovascular Diseases | Investigative Techniques
Background: Prior studies relating proteomics markers to incident AF screened for limited numbers of proteins.
Methods and Results: We performed proteomics assays among participants from the Framingham Heart Study Offspring attending their fifth examination. Plasma protein levels (n=1373) were measured by the SOMAscan proteomic profiling platform. We used robust inference for the Cox proportional hazards model to relate each protein level with incident AF. In addition, we examined the association between AF-related genetic loci and levels of proteins associated with AF. Our study included 1885 participants (mean age 55+/-10 years, 54% women) who had proteomic profiles measured. A total of 349 participants developed AF during follow-up (mean follow-up 18.3 years). We observed that 8 proteins were significantly associated with incident AF after adjusting for age, sex, technical covariates, and correction for multiple testing ( P < 0.05/1373=3.6x10(-5)). After additional adjustments for clinical factors associated with AF, ADAMTS13 and N-terminal pro-B-type natriuretic peptide remained significantly associated with the risk of incident AF (hazard ratio, 0.78; 95% CI, 0.70-0.88; and 1.44; 95% CI, 1.22-1.70, respectively; P < 3.6x10(-5) for both). None of the 8 proteins were encoded by genes at AF-related genetic loci previously identified by genome-wide association studies.
Conclusions: We identified 8 proteins associated with risk of incident AF after adjustment for age and sex; 2 proteins were associated with AF after adjustment for AF risk factors. Future studies are needed to replicate our findings, identify whether the markers are mechanistically related to AF development, and whether they are clinically useful for identification of future AF risk.
atrial fibrillation, biomarker, proteomics, risk
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Copyright 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercial and no modifications or adaptations are made.
DOI of Published Version
J Am Heart Assoc. 2019 Mar 19;8(6):e010976. doi: 10.1161/JAHA.118.010976. Link to article on publisher's site
Journal of the American Heart Association
Ko, Darae; Benson, Mark D.; Ngo, Debby; Yang, Qiong; Larson, Martin G.; Wang, Thomas J.; Trinquart, Ludovic; McManus, David D.; Lubitz, Steven A.; Ellinor, Patrick T.; Vasan, Ramachandran S.; Gerszten, Robert E.; Benjamin, Emelia J.; and Lin, Honghuang, "Proteomics Profiling and Risk of New-Onset Atrial Fibrillation: Framingham Heart Study" (2019). Open Access Articles. 3793.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.